The plasma membrane Na+/Ca2+ exchanger is cleaved by distinct protease families in neuronal cell death
The plasma membrane Na+/Ca2+ exchanger is cleaved by distinct protease families in neuronal cell death
复制标题
DOI：
10.1196/annals.1387.006
复制
发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Nicotera, P.
中科院分区：
文献类型：
--
作者：
Bano, D.;Munarriz, E.;Nicotera, P.
神经退行性疾病通常包括神经元连接的丧失，过度修剪的突触功能障碍，以及离子失衡。这些通常作为细胞死亡的前奏，要么通过激活凋亡或坏死性死亡例程，要么通过过度的自噬。在许多情况下，局部或普遍的钙离子去调节参与了细胞死亡的信号传递或执行。我们最近的研究表明，在脑缺血和谷氨酸过量引发的兴奋性毒性中，导致坏死的不可逆的钙离子释放是由于钙蛋白介导的质膜Na~+/Ca~(2+)交换器(NCX)的调节。在这里，我们发现NCX也可以被caspase切割，这表明在多种形式的细胞死亡中，主要的Ca~(2+)排出途径的切割是一个致命事件。
Neurodegenerative conditions commonly involve loss of neuronal connectivity, synaptic dysfunction with excessive pruning, and ionic imbalances. These often serve as a prelude to cell death either through the activation of apoptotic or necrotic death routines or excess autophagy. In many instances, a local or generalized Ca2+ deregulation is involved in signaling or executing cell death. We have recently shown that in brain ischemia, and during excitotoxicity triggered by excess glutamate, the irreversible Ca2+ deregulation leading to necrosis is due to calpain-mediated modulation of the plasma membrane Na+/Ca2+ exchanger (NCX). Here we show that the NCX can also be cleaved by caspases in neurons undergoing apoptosis, which suggests that cleavage of the main Ca2+ extrusion pathway is a lethal event in multiple forms of cell death.